Topotecan in Treating Patients With Recurrent Extensive-Stage Small Cell Lung Cancer

The Use Of Weekly Topotecan As Second Line Therapy In Small Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well high-dose topotecan works as second-line therapy in treating patients with recurrent extensive-stage small cell lung cancer.

OBJECTIVES:

Primary

• Determine the overall survival of patients with recurrent extensive stage small cell lung cancer treated with high-dose topotecan hydrochloride.

Secondary

• Determine the safety and toxic effects of this drug in these patients.
• Determine the recurrence-free survival of patients treated with this drug.
• Determine time to response and tumor response in patients treated with this drug.
• Determine the quality of life of patients treated with this drug.

OUTLINE: This is a non-randomized, multicenter study.

Patients receive high-dose topotecan hydrochloride IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 56 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, day 1 of each course (except course 1), at the end of study treatment, and then every 3 months thereafter.

Patients are followed at 7-14 days and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed small cell lung cancer (SCLC)

  • Recurrent extensive stage disease
  • No mixed histology

• Measurable disease

  • At least 1 bidimensionally measurable, non-central nervous system (CNS), indicator lesion confirmed by CT scan or MRI

• Sensitive disease

  • Responded to prior first-line therapy AND relapsed ≥ 60 days after response (90 days after initiation of first-line therapy)

• Eligible for high-dose chemotherapy

• No symptomatic brain metastases affecting performance status

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Eastern Cooperative Oncology Group (ECOG) 0-2

Life expectancy

• At least 2 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL
• Hematocrit > 35% (without transfusion)

Hepatic

• Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) ≤ 2 times normal*
• Alkaline phosphatase ≤ 2 times normal*
• Bilirubin ≤ 2.0 mg/dL
• Albumin > 2.5 g/dL
• Hepatitis B surface antigen negative
• No significant hepatic disease Note: *≤ 5 times upper limit of normal if liver metastases are present

Renal

• Creatinine clearance ≥ 40 mL/min

Cardiovascular

• No history of cardiac arrhythmias
• No congestive heart failure
• No ischemic heart disease
• No stroke or other embolic disease requiring daily treatment that would preclude study participation

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• HIV negative
• No known seizure disorder
• No active infection requiring systemic therapy within the past 2 weeks
• No known hypersensitivity to topotecan hydrochloride
• No medical or psychiatric condition that would preclude study participation
• No other malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or stage A low-grade prostate cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior antineoplastic and/or myelosuppressive chemotherapy
• No more than 1 prior chemotherapy regimen (except for adjuvant chemotherapy) for SCLC
• No prior topotecan hydrochloride

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 2 months since prior investigational agent
• No other concurrent investigational agent